Journal
EXPERIMENTAL CELL RESEARCH
Volume 373, Issue 1-2, Pages 99-111Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2018.10.002
Keywords
Blood-brain barrier; Transendothelial migration; alpha(5)beta(1 )integrin; Fibronectin; Actin; FAK; Src
Categories
Funding
- Sonnenfeld-Stiftung (Berlin, Germany)
- Free University Berlin (Berlin, Germany)
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS091102] Funding Source: NIH RePORTER
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Neuroinflammation is often associated with pathological changes in the function of the blood-brain barrier (BBB) caused by disassembly of tight and adherens junctions that under physiological conditions are important for the maintenance of the BBB integrity. Consequently, in inflammation the BBB becomes dysfunctional, facilitating leukocyte traversal of the barrier and accumulation of immune cells within the brain. The extracellular matrix (ECM) also contributes to BBB integrity but the significance of the main ECM receptors, the beta(1) integrins also expressed on endothelial cells, is less well understood. To evaluate whether beta(1) integrin function is affected during inflammation and impacts barrier function, we used a transformed human brain microvascular endothelial cell (THBMEC)-based Interleukin 1 beta (IL-1 beta)-induced inflammatory in vitro BBB model. We demonstrate that IL-1 beta increases cell-matrix adhesion and induces a redistribution of active beta(1) integrins to the basal surface. In particular, binding of alpha(5)beta(1) integrin to its ligand fibronectin is enhanced and alpha(5)beta(1) integrin-dependent signalling is upregulated. Additionally, localisation of the tight junction protein claudin-5 is altered. Blockade of the alpha(5)beta(1) integrin reduces the IL-1 beta-induced transendothelial migration of peripheral blood mononuclear cells (PBMCs). These data imply that IL-1 beta-induced inflammation not only destabilizes tight junctions but also increases alpha(5)beta(1) integrin-dependent cell-matrix adhesion to fibronectin.
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